When trying to understand how genetic influences factor into youth behavior, researchers at Washington University in St. Louis have taken the “big trawl” approach, casting their net wide to pull in all the measured traits, behaviors and environments that make up who we are and examine associations with the genetic building blocks comprising risk for mental health problems.
This cutting-edge methodology has turned up valuable new insights into factors related to psychopathological genetic risk, such as stressful life events and screen time. Although the results, published in Nature Mental Health, are unable to say if one causes the other, the findings provide promising leads to understand the nature of psychiatric disorders emerging during adolescence.
“We’re catching all the little fish here,” said Nicole Karcher, PhD, an assistant professor of psychiatry at WashU Medicine, likening their genetic screening tools to trawling the ocean.
“But now we get to wade through the fish that we caught, and future steps include understanding the extent to which these are meaningful in terms of their ability to reduce risk for mental health concerns.”
Much of what we know about links between the genome and behavior come from Genome-wide Associations Studies (GWAS), which identify links between specific genetic variants across the genome and a feature of interest, also known as a phenotype. Phenotypes can range from physical characteristics to psychiatric disorders (e.g., depression and anxiety).
Many behavioral disorders are correlated at the genetic level. Results from a GWAS scanning for genetic links to depression, therefore, may also reflect genetic associations with frequently co-occurring conditions such as anxiety.
“We know that one behavioral variable is not going to be the only association with genetic risk, so we were interested in taking a more agnostic, data-driven approach to the wealth of information that is available in large datasets,” Karcher said.
Doing so would hopefully identify not only expected associations between genetic risk and psychiatric symptoms, but also potential novel associations that could improve insight into how psychiatric disorder risk may unfold.
So senior author Karcher and first author Sarah Paul, a graduate student in Ryan Bogdan’s Behavioral Research and Imaging Neurogenetics Laboratory in Arts & Sciences, ran what’s called a phenome-wide association study (PheWAS) that inverts the GWAS.